Aripiprazole, a novel antipsychotic drug, inhibits quinpriole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum

Inoue, Atsuko; Miki, Sinya; Seto, Mayumi; Kikuchi, Tetsuro; Morita, Seiji; Ueda, Hiroshi; Misu, Yoshimi; Nakata, Yoshihiro

doi:10.1016/s0014-2999(96)00920-x

Cited by 98 publications

(71 citation statements)

References 22 publications

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“…It has been reported that chronic neuroleptic administration results in the upregulation of dopamine D 2 receptors in animal models (Burt et al 1977;Clow et al 1979;1980a,b;Murugaiah et al 1985;Theodorou et al 1981). Interestingly, repeated aripiprazole administration does not lead to significant receptor upregulation in the rat striatum (Inoue et al 1997). This could suggest that receptor occupancy by conventional neuroleptics measured with PET might be underestimated in the chronically medicated state caused by upregulation of dopamine D 2 receptors in the brain, which may not occur with aripiprazole.…”

Section: Discussionmentioning

confidence: 99%

“…These in vivo properties are consistent with the biochemical characterization of partial agonist activity. In addition, aripiprazole has been shown to exhibit partial agonist properties, ex vivo, via the inhibition of spontaneous prolactin release from isolated rat anterior pituitary slices (Inoue et al 1996) and does not appear to upregulate D 2 receptors following repeated administration (21 days; Inoue et al 1997). In cloned transfected cell lines, aripiprazole exhibits high affinity for D 2 (K i ϭ 0.8 nM) and D 3 dopamine receptors (K i ϭ 13 nM), a lower affinity for the D 4 receptor (K i of approximately 200 nM), and negligible affinity for D 1 -like dopamine receptors.…”

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confidence: 99%

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Dopamine D2 and D3 Receptor Occupancy in Normal Humans Treated with the Antipsychotic Drug Aripiprazole (OPC 14597) A Study Using Positron Emission Tomography and [11C]Raclopride

Yokoi

2002

Neuropsychopharmacology

279

147

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dopamine D2 and D3 Receptor Occupancy in Normal Humans Treated with the Antipsychotic Drug Aripiprazole (OPC 14597) A Study Using Positron Emission Tomography and [11C]Raclopride

Yokoi

2002

Neuropsychopharmacology

279

147

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“…While aripiprazole has high affinity for D 2 receptors, it has low intrinsic efficacy (15,89). Aripiprazole has been touted as a "dopamine system stabilizer" (48,79,82) because in vivo studies demonstrate that it reduces dopamine release via presynaptic agonism (49) to behave as a functional antagonist of some postsynaptic D 2 -receptors (49) and as an agonist at others (38).…”

Section: Dopamine (Da) Receptor Activitymentioning

confidence: 99%

Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology

2004

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Aripiprazole (Abilify ® ) is an atypical antipsychotic drug that has been recently introduced for clinical use in the treatment of schizophrenia. Aripiprazole has a unique pharmacologic profile that includes partial agonism at several G-protein coupled receptors (GPCRs) [especially dopamine (D 2 ) and 5-HT 1A ] and antagonistic action at others (especially 5-HT 2A ). Clinical trials indicate that aripiprazole is effective in treating the positive and negative symptoms of schizophrenia. In short-term studies rapid onset of action (within one week) has been demonstrated. Preliminary data indicate that aripiprazole may also be effective in the treatment of manic symptoms of bipolar disorder. At recommended doses, aripiprazole appears to be safe and well tolerated in most adult patients with schizophrenia and schizoaffective disorder. There is only limited information available on the use of aripiprazole in children and adolescents, and pilot data suggest that a revised dosing strategy, based on weight, is indicated in this population. In the long-term studies, the use of aripiprazole was associated with continued efficacy, good compliance and increased time-to-relapse.Aripiprazole represents the first functionally selective atypical antipsychotic drug.

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“…OPC-14597 has been reported to produce minimal increases in D 2 receptor density following chronic treatment in rat (Inoue et al 1997). Moreover, OPC-14597 shares some characteristics of other atypical antipsychotics with respect to induction of early immediate gene expression.…”

Section: Cells; C-6 Cells; Schizophreniamentioning

confidence: 99%

Interactions of the Novel Antipsychotic Aripiprazole (OPC-14597) with Dopamine and Serotonin Receptor Subtypes

Lawler

Prioleau

Lewis

et al. 1999

Neuropsychopharmacology

377

298

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cells; C-6 cells; SchizophreniaSchizophrenia is a chronic psychiatric illness with two major types of symptoms-positive or psychotic symptoms, such as hallucinations and delusions, and negative or deficit symptoms, such as amotivation, apathy, and asociality. Approximately 1% of the population suffers from schizophrenia (Kaplan and Sadock 1988). The serendipitous discovery of chlorpromazine four decades ago not only provided the first efficacious therapeutic intervention, but also opened horizons into research about the etiology and therapy of this disease. It was soon hypothesized that chlorpromazine and similar drugs worked by being pharmacological antagonists of the neurotransmitter dopamine (Seeman et al. 1976;Creese et al. 1976), a hypothesis that ultimately provided the foundation for the commonly accepted division of dopamine receptors into two classes (Garau et al. 1978), now often called D 1 and D 2 (Kebabian and Calne 1979).During the past decade, molecular cloning studies have resulted in the identification of several genes coding for dopamine receptors. There now are at least two From the Departments of Pharmacology (CP, RBM) and Psychiatry (CPL, RBM), and Medicinal Chemistry (RBM), Curricula in Toxicology (CPL, RBM), and Neurobiology (MML, RBM), UNC Neuroscience Center (CPL, CP, MML, RBM), University of North Carolina School of Medicine, Chapel Hill, North Carolina; and Molecular Neuropharmacology Section (CM, DJ, JAS, AMG, DRS), National Institutes of Neurological Disorders and Stroke, Bethesda, Maryland.Address correspondence to: Dr. Cindy Lawler, CB #7250; UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7250. Received April 17, 1998; revised August 27, 1998; accepted September 21, 1998. (Zhou et al. 1990;Monsma et al. 1990;Sunahara et al. 1990;Dearry et al. 1990) and D 1B (Tiberi et al. 1991) or D 5 (Sunahara et al. 1991], both of these linked functionally to stimulation of cAMP synthesis, and preferentially recognizing 1-phenyl-tetrahydrobenzazepines (e.g., SCH23390). The D 2 -like receptors come from at least three genes and include multiple splice variants. The D 2 -like receptors [D 2S (Bunzow et al. 1988), D 2L (Giros et al. 1989;Monsma et al. 1989), D 3 (Sokoloff et al. 1990, and D 4 ] sometimes are linked to inhibition of cAMP synthesis and have a different pharmacological specificity from the D 1 -like receptors (i.e., having much higher affinity for spiperone or sulpiride).The traditional view of antipsychotic drug efficacy posits a primary role for pharmacological antagonism of D 2 -like receptors. Despite the demonstrable effectiveness of dopamine D 2 receptor antagonists, however, a substantial number (up to 20%) of patients are considered unresponsive to these typical antipsychotics (Kane et al. 1988). Furthermore, the typical antipsychotics have significant and serious side effects that make them less than optimal therapeutic agents (see Peacock and Gerlach 1996). For example, they cause acute drug-induced parkinsonian symptoms (...

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Aripiprazole, a novel antipsychotic drug, inhibits quinpriole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum

Cited by 98 publications

References 22 publications

Dopamine D2 and D3 Receptor Occupancy in Normal Humans Treated with the Antipsychotic Drug Aripiprazole (OPC 14597) A Study Using Positron Emission Tomography and [11C]Raclopride

Dopamine D2 and D3 Receptor Occupancy in Normal Humans Treated with the Antipsychotic Drug Aripiprazole (OPC 14597) A Study Using Positron Emission Tomography and [11C]Raclopride

Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology

Interactions of the Novel Antipsychotic Aripiprazole (OPC-14597) with Dopamine and Serotonin Receptor Subtypes

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